Catheter-based in vivo imaging of enzyme activity and gene expression: Feasibility study in mice
Catheter-based in vivo imaging of enzyme activity and gene expression: Feasibility study in mice
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DOI：
10.1148/radiol.2313030831
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发表时间：
2004-06-01
期刊：
影响因子：
19.7
通讯作者：
Mahmood, U
中科院分区：
文献类型：
--
作者：
Funovics, MA;Weissleder, R;Mahmood, U
目得：构建和评估一个基于介入导管的成像系统，用于活体监测的分子敏感的近红外荧光探针和光学标记genes.MATERIALS和METHODS：一个成像设备，这是基于一个小型化的光纤传感器（MIFS）内置的图像创建一个2.7-F的光纤导管被中继通过分色镜，通过带通滤波器，并在两个独立的摄像机。该系统允许同时记录白光和荧光图像。在体外测定空间分辨率、光谱透射率和灵敏度。在表达绿色荧光蛋白的腹腔内肿瘤裸鼠和卵巢癌小鼠模型中，用对肿瘤蛋白酶活性敏感的酶激活近红外探针进行体内试验。测量肿瘤图像和正常组织图像上的信号强度，并进行t检验。结果：该导管的分辨率为7线对/mm，荧光染料CyS.S的检测限为1-10 pmol。内源性绿色荧光蛋白基因表达的检测在直径小于1 mm的肿瘤结节中是可行的（平均肿瘤信号强度为153.26 ± 26.45 [SD]，与邻近非肿瘤组织的36.73 ± 11.69相比; P <0.008）。同样，在卵巢癌模型的腹膜肿瘤种子中可以检测到肿瘤蛋白酶对近红外探针的激活，平均肿瘤信号强度为246.33 +/- 7.77，而邻近非肿瘤组织的平均信号强度为41.56 +/- 18.64（P <0.001）。近红外通道的平均对比度噪声比超过白光对比度噪声比的6.7倍（P <0.02）。结论：使用该系统，通过直接介入进入几个器官和体腔，并可能通过经血管方法，体内MIFS成像的基因表达，酶活性和潜在的其他分子事件是可行的。(C)RSNA，2004年。
PURPOSE: To construct and evaluate an interventional catheter-based imaging system for intravital monitoring of molecularly sensitive near-infrared fluorescent probes and optical marker genes.MATERIALS AND METHODS: An imaging device that was based on a miniaturized fiberoptic sensor (MIFS) was built in which images created with a 2.7-F fiberoptic catheter were relayed through a dichroic mirror, through a bandpass filter, and on two independent cameras. This system permitted simultaneous recording of white-light and fluorescent images. Spatial resolution, spectral transmissions, and sensitivity were determined in vitro. In vivo testing was performed in nude mice bearing intraperitoneal tumors that express green fluorescent protein and in a mouse model of ovarian carcinoma with enzyme-activatable near-infrared probes sensitive to tumoral protease activity. Signal intensity on images of tumors and that on images of normal tissue were measured and compared with t test. which was advanced through an 18-gauge sheath,RESULTS: The catheter, showed resolution of 7 line pairs per millimeter and detection limit for fluorochrome CyS.S of 1-10 pmol. Detection of endogeneous green fluorescent protein gene expression was feasible in tumor nodules smaller than I mm in diameter (mean tumor signal intensity, 153.26 +/- 26.45 [SD], compared with that of adjacent nontumoral tissue of 36.73 +/- 11.69; P < .008). Similarly, activation of the near-infrared probe by tumoral proteases could be detected in peritoneal tumor seeds of ovarian cancer model with mean tumor signal intensity of 246.33 +/- 7.77 compared with that of adjacent nontumoral tissue of 41.56 +/- 18.64 (P < .001). Mean contrast-to-noise ratio in the near-infrared channel exceeded white-light contrasts-to-noise ratio by a factor of 6.7 (P < .02).CONCLUSION: With this system, in vivo MIFS imaging of gene expression, enzyme activity, and potentially other molecular events is feasible, through direct interventional access, to several organs and body cavities and potentially through transvascular approaches. (C) RSNA, 2004.